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Exogenous D-ribose promotes gentamicin treatment of several drug-resistant Salmonella

The metabolic microenvironment of bacteria impacts drug efficacy. However, the metabolic mechanisms of drug-resistant Salmonella spp. remain largely unknown. This study characterized the metabolic mechanism of gentamicin-resistant Salmonella Choleraesuis and found that D-ribose increased the gentami...

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Autores principales: Zhou, Yanhong, Yong, Yan, Zhu, Chunyang, Yang, Heng, Fang, Binghu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9676500/
https://www.ncbi.nlm.nih.gov/pubmed/36419438
http://dx.doi.org/10.3389/fmicb.2022.1053330
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author Zhou, Yanhong
Yong, Yan
Zhu, Chunyang
Yang, Heng
Fang, Binghu
author_facet Zhou, Yanhong
Yong, Yan
Zhu, Chunyang
Yang, Heng
Fang, Binghu
author_sort Zhou, Yanhong
collection PubMed
description The metabolic microenvironment of bacteria impacts drug efficacy. However, the metabolic mechanisms of drug-resistant Salmonella spp. remain largely unknown. This study characterized the metabolic mechanism of gentamicin-resistant Salmonella Choleraesuis and found that D-ribose increased the gentamicin-mediated killing of this bacteria. Non-targeted metabolomics of homologous gentamicin-susceptible Salmonella Choleraesuis (SCH-S) and gentamicin-resistant S. Choleraesuis (SCH-R) was performed using UHPLC-Q-TOF MS. The metabolic signature of SCH-R included disrupted central carbon metabolism and energy metabolism, along with dysregulated amino acid and nucleotide metabolism, vitamin and cofactor metabolism, and fatty acid synthesis. D-ribose, the most suppressed metabolite in SCH-R, was shown to strengthen gentamicin efficacy against SCH-R and a clinically isolated multidrug-resistant strain. This metabolite had a similar impact on Salmonella. Derby and Salmonella. Typhimurium. D-ribose activates central carbon metabolism including glycolysis, the pentose phosphate pathway (PPP), and the tricarboxylic acid cycle (TCA cycle), increases the abundance of NADH, polarizes the electron transport chain (ETC), and elevates the proton motive force (PMF) of cells, and induces drug uptake and cell death. These findings suggest that central carbon metabolism plays a critical role in the acquisition of gentamicin resistance by Salmonella, and that D-ribose may serve as an antibiotic adjuvant for gentamicin treatment of resistant bacterial infections.
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spelling pubmed-96765002022-11-22 Exogenous D-ribose promotes gentamicin treatment of several drug-resistant Salmonella Zhou, Yanhong Yong, Yan Zhu, Chunyang Yang, Heng Fang, Binghu Front Microbiol Microbiology The metabolic microenvironment of bacteria impacts drug efficacy. However, the metabolic mechanisms of drug-resistant Salmonella spp. remain largely unknown. This study characterized the metabolic mechanism of gentamicin-resistant Salmonella Choleraesuis and found that D-ribose increased the gentamicin-mediated killing of this bacteria. Non-targeted metabolomics of homologous gentamicin-susceptible Salmonella Choleraesuis (SCH-S) and gentamicin-resistant S. Choleraesuis (SCH-R) was performed using UHPLC-Q-TOF MS. The metabolic signature of SCH-R included disrupted central carbon metabolism and energy metabolism, along with dysregulated amino acid and nucleotide metabolism, vitamin and cofactor metabolism, and fatty acid synthesis. D-ribose, the most suppressed metabolite in SCH-R, was shown to strengthen gentamicin efficacy against SCH-R and a clinically isolated multidrug-resistant strain. This metabolite had a similar impact on Salmonella. Derby and Salmonella. Typhimurium. D-ribose activates central carbon metabolism including glycolysis, the pentose phosphate pathway (PPP), and the tricarboxylic acid cycle (TCA cycle), increases the abundance of NADH, polarizes the electron transport chain (ETC), and elevates the proton motive force (PMF) of cells, and induces drug uptake and cell death. These findings suggest that central carbon metabolism plays a critical role in the acquisition of gentamicin resistance by Salmonella, and that D-ribose may serve as an antibiotic adjuvant for gentamicin treatment of resistant bacterial infections. Frontiers Media S.A. 2022-11-07 /pmc/articles/PMC9676500/ /pubmed/36419438 http://dx.doi.org/10.3389/fmicb.2022.1053330 Text en Copyright © 2022 Zhou, Yong, Zhu, Yang and Fang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Zhou, Yanhong
Yong, Yan
Zhu, Chunyang
Yang, Heng
Fang, Binghu
Exogenous D-ribose promotes gentamicin treatment of several drug-resistant Salmonella
title Exogenous D-ribose promotes gentamicin treatment of several drug-resistant Salmonella
title_full Exogenous D-ribose promotes gentamicin treatment of several drug-resistant Salmonella
title_fullStr Exogenous D-ribose promotes gentamicin treatment of several drug-resistant Salmonella
title_full_unstemmed Exogenous D-ribose promotes gentamicin treatment of several drug-resistant Salmonella
title_short Exogenous D-ribose promotes gentamicin treatment of several drug-resistant Salmonella
title_sort exogenous d-ribose promotes gentamicin treatment of several drug-resistant salmonella
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9676500/
https://www.ncbi.nlm.nih.gov/pubmed/36419438
http://dx.doi.org/10.3389/fmicb.2022.1053330
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